PHARMACOLOGICALLY ACTIVE COMPOUNDS AS INHIBITORS OF THE TAM FAMILY RECEPTOR TYROSINE KINASE Russian patent published in 2021 - IPC C07D401/14 C07D401/12 C07D405/14 C07D409/14 C07D413/14 C07D417/14 A61K31/4709 A61K31/497 A61K31/501 A61K31/506 A61K45/06 A61P35/00 A61P35/02 A61P35/04 

FIELD: organic chemistry.

SUBSTANCE: present invention relates to new compounds that are inhibitors of the receptor tyrosine kinase (RTK) family and Met and have general formula I, in which X¹ is in each case independently selected from CH and N; X² is in each case independently selected from CH and N; Y¹ is in each case independently selected from СН₂, СН(СН₃)СН₂, С(СН₃)₂, С(СН₃)₂СН₂ and СН₂СН₂; n is in each case independently selected from 0 and 1; R¹ is in each case independently selected from a group consisting of С1-С6 alkyl and С1-С3 haloalkyl; R² is in each case independently selected from a group consisting of С1-С6 alkyl and С1-С3 haloalkyl; R³ is in each case independently selected from a group consisting of hydrogen, halogen, С1-С3 alkyl and NHCH(CH₃)CH₃; R⁴ is in each case independently selected from a group consisting of hydrogen, halogen, -СН₂ОН and -CF₃; R⁵ is in each case independently selected from a group consisting of С1-С6 alkyl, С1-С6 alkyl substituted with C3-C6 cycloalkyl, oxetanyl, azetidinyl, or O-(C1-C6 alkyl), С1-С3 haloalkyl, N,N-dimethylethanamino, N,N-dimethylpropane-1-amino; R⁶ is in each case independently selected from a group consisting of hydrogen and СН₃; Z¹ is in each case independently selected from a group consisting of hydrogen, hydroxyl, C1-C6 alkyl, C(O)R⁷, C(O)NHR⁷, C(O)OR⁷, CN, N(R⁷)₂, OR⁷, OCH₂F, OCHF₂, OCF₃ and any structure from group A (see Cl.1 of the formula); R⁷ is in each case independently selected from a group consisting of hydrogen and С1-С6 alkyl; R⁹ is in each case independently selected from a group consisting of hydrogen, С1-С6 alkyl, С3-С6 cycloalkyl; C1-C6 alkenyl, heterocyclyl, C1-C3 haloalkyl, C(O)OR⁷, CH₂C(O)OR⁷, C(O)R⁷, -(CH₂)_mNR⁷R¹³, -(CH₂)_mOR⁷, C1-C3 alkoxy, haloalkoxy, phenoxy, С(СН₃)₂ОН, С(СН₃)(ОН)СН₂ОН, F, Cl, NH₂, CN, phenyl, pyrrolidinyl, m is an integer, independently selected in each case from 0, 1, 2, and 3; R¹⁰ is in each case independently selected from a group consisting of hydrogen, hydroxyl, halogen, С1-С6 alkyl, C1-C3 haloalkyl, C(O)R⁷, CH₂NR⁷R¹³, CH₂OH, C(O)NR⁷R¹³ and CN; R¹¹ is in each case independently selected from a group consisting of hydrogen, hydroxyl, С1-С6 alkyl, С1-С3 haloalkyl, C(O)OR⁷, C(CH₃)₂(CH₂)_mNR⁷R¹³, -(CH₂)_mNR⁷R¹³, CH₂OH, C₁-C₃ alkoxy, haloalkoxy, halogen, CN, NH₂, -(CH₂)_m heteroaryl, -NH(C₁-C₆ alkyl), m is an integer independently in each case selected from 0, 1, 2 and 3; R¹² is in each case independently selected from a group consisting of hydrogen, halogen, С1-С6 alkyl; С3-С6 cycloalkyl, heterocycloalkyl, -(CH₂)_mNR⁷R¹³, wherein m is an integer independently in each case selected from 0, 1, 2 and 3; R¹³ is in each case independently selected from a group consisting of hydrogen and С1-С6 alkyl, СОМe, CONH₂ (subject to restrictions, see Cl. 1 of the formula). In addition, compounds with inhibitory activity against the receptor tyrosine kinase of the TAM and Met families and having general formula V, wherein the values of the radicals are indicated in the claims, and their pharmacologically acceptable salts are described. In addition, the use of these compounds as a pharmacologically active agent and a pharmaceutical composition based on the described compounds are described for the treatment of disorders accompanied, caused or induced by the TAM family receptor, in particular its hyperfunction.

EFFECT: new compounds have been obtained and described that are suitable for the treatment of hyperproliferative disorders such as cancer, in particular immunosuppressive cancer, refractory cancer and cancer metastases.

32 cl, 4 tbl